Microwave-assisted three-component cyclocondensation of thiourea, ethyl acetoacetate, and substituted benzaldehydes

Full text of DOI:10.1134/S1070363212020272

ISSN 1070-3632, Russian Journal of General Chemistry, 2012, Vol. 82, No. 2, pp. 338–339. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © S.D. Fazylov, A.E. Arinova, O.A. Nurkenov, A.V. Boldashevskii, 2012, published in Zhurnal Obshchei Khimii, 2012, Vol. 82, No. 2,
pp. 343–344.
LETTERS
TO THE EDITOR
Microwave-Assisted Three-Сomponent Cyclocondensation
of Thiourea, Ethyl Acetoacetate,
and Substituted Benzaldehydes
S. D. Fazylov, A. E. Arinova, O. A. Nurkenov, and A. V. Boldashevskii
Institute of Organic Synthesis and Coal Chemistry of the Republic of Kazakhstan
ul. Alikhanova 1, Karaganda, 100008 Kazakhstan
e-mail: faziosu@rambler.ru
Received September 8, 2011
DOI: 10.1134/S1070363212020272
A typical Biginelli reaction involving ethyl
acetoacetate, aldehyde, and thiourea under the standard
conditions is carried out in the presence of hydro-
chloric or sulfuric acid, more preferred is the use of
inorganic salts, the Lewis acids [1]. The main draw-
back is the long reaction time. We investigated the
three-component condensation of thiourea, ethyl aceto-
acetate, and p-substituted benzaldehyde derivatives in
the Biginelli reaction either at the simple heating or
microwave irradiation. If the reaction is carred out in
the boiling ethyl alcohol using MnCl2·H2O as a
catalyst, it is completed within 6–8 h. The use of
microwave irradiation makes it possible to reduce the
reaction time to 150 min at 750 W.
S
O
HN C
O
H
MnCl2
DMF
4 H2O
NH2
NH2
O
C
+
CH3
C
R
NH
+
R
C
C
S
CH2
OC2H5
O
CH3
OC2H5
I−III
R = H (I), OCH (II),
(III).
O
N
3
The optimization of the reaction conditions was
carried out by varying the reaction time (from 1 to
180 min) and the irradiation power (from 75 to 750 W)
with a frequency of 2450 MHz (LG MS2022G) in the
medium of solvents like ethanol and dimethylform-
amide.
synthetic features can be attributed to the behavior in
the microwave field [4].
1
The H NMR spectra of compounds I–III were
recorded on a Bruker AM-400 spectrometer in DMSO-
d6 using TMS as a reference. The purity of the com-
pounds obtained was monitored by TLC (Silufol UV-
254, eluent CHC13–EtOH). The melting points were
determined on a Boetius melting point apparatus.
The structure of the obtained 5-(ethoxycarbonyl)-4-
(4-R-phenyl)-6-methyl-3,4-di-hydropyrimidine-2(1H)-
thiones I–III) was confirmed by the analytical and
spectral data, which were consistent with those of the
other 3,4-dihydropyrimidinethiones [1–3]. Thus, the
behavior of the reaction components under the
microwave irradiation conditions does not differ from
that under the conventional heating conditions. Some
5-Ethoxycarbonyl-4-phenyl-6-methyl-3,4-dihyd-
ropyrimidine-2(1H)-thione (I). A mixture of 0.55 g
of benzaldehyde, 0.48 g of ethyl acetoacetate, 0.3 g of
thiourea, 0.25 g of MnCl2·4H2O, and 50 ml of DMF
was subjected to microwave irradiation for 150 min
with intermissions. After cooling, the resulting pre-
338

MICROWAVE-ASSISTED THREE-СOMPONENT CYCLOCONDENSATION
339
cipitate was filtered off, washed with water, dried, and
recrystallized from ethanol. Yield 0.63 g (62%), mp
263–264oС. 1Н NMR spectrum (DMSO-d6), δ, ppm:
1.10–1.13 t (3Н, СН3СН2О), 2.27 s (3Н, СН3С), 3.05–
1
208–210oС. Н NMR spectrum (DMSO-d6), δ, ppm:
3.09
t
(2H, NCH2CH2O), 3.70–3.73
t
(2H,
1.08–1.12 t (3Н, СН3СН2О), 2.29 s (3Н, СН3С), 4.03
q (2Н, СН3СН2О, J 7.2 Hz), 5.09 s (1Н, NCHAr),
5.16–5.21 d (2Н, СНAr, J 8.0 Hz ), 7.33–7.37 d (2Н,
СНAr, J 8.0 Hz), 9.63 s (1Н, NH), 10.31 s (1Н, NH).
Found, %: С 60.91; N 10.20. С14H16N2O2S. Calculated,
%: С 60.85; N 10.14.
NCH2CH2O), 3.98–4.03 q (2Н, СН3СН2О), 5.07 d
(1Н, NCHAr), 6,89 d (2Н, СНAr, J 8.0 Hz), 7.06 d
(2Н, СНAr, J 8.6 Hz), 9.56 br. s (1Н, NH), 10.20 s (1Н,
NH). Found, %: С 59.96; N 11.75. С18H23N3O3S.
Calculated, %: С 59.81; N 11.63.
REFERENCES
5-Ethoxycarbonyl-4-(4-methoxyphenyl)-6-methyl-
3,4-dihydropyrimidine-2(1H)-thione (II) was syn-
thesized similarly. Yield 0.58 g (50%), mp 152–153oС.
1Н NMR spectrum (DMSO-d6), δ, ppm: 1.10 t (3Н,
СН3СН2О), 2.24 s (3Н, СН3С), 3.71 t (2H,
NCH2CH2O), 3.98 q (2Н, СН3СН2О, J 7.0 Hz), 5.09 s
(1Н, NCHAr), 6.88 d (2Н, СНAr, J 8.0 Hz ), 7.15 d
(2Н, СНAr, J 8.4 Hz), 9.17 br. s (1Н, NH), 10.25 s (1Н,
NH). Found, %: С 58.95; N 9.03. С15H18N2O3S.
Calculated, %: С 58.80; N 9.14.
1. Vdovina, V.S. and Mamedov, V.A., Usp. Khim., 2008,
vol. 77, no. 5, p. 1091.
2. D’yachenko, E.V., Glukhareva, T.V., Nikolaenko, E.F.,
Tkachev, A.V., and Morzherin, Yu.Yu., Izv. Akad. Nauk
SSSR, Ser. Khim., 2004, no. 6, p. 1191.
3. Potkin, V.I., Petkevich, S.K., Kaberdin, R.V., and
Kurman, P.V., Zh. Org. Khim., 2002, vol. 38, p. 1150.
4. Fazylov, S.D., Khrustalev, D.P., Muldakhmetov, Z.M.,
and Boldashevskii, A.V., Reaktsii organicheskogo
sinteza
v usloviyakh mikrovolnovogo oblucheniya
5-Ethoxycarbonyl-4-(4-morpholinophenyl)-6-
methyl-3,4-dihydropyrimidine-2(1H)-thione (III)
was synthesized similarly. Yield 1.05 g (81%), mp
(Organic Synthesis Reactions under Microwave Irra-
diation Conditions), Karaganda; Pavlodar: Izd. Pavlo-
darskogo Pedinstituta, 2010.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 2 2012